title: Mitogen-activated protein kinase phosphatase 1 as an inflammatory factor and drug target.
abstract: Mitogen-activated protein kinases (MAPKs) are signaling proteins that are activated through phosphorylation, and they regulate many physiological and pathophysiological processes in cells. Mitogen-activated protein kinase phosphatase 1 (MKP-1) is an inducible nuclear phosphatase that dephosphorylates MAPKs, and thus, it is a negative feedback regulator of MAPK activity. MKP-1 has been found as a key endogenous suppressor of innate immune responses, as well as a regulator of the onset and course of adaptive immune responses. Altered MKP-1 signaling is implicated in chronic inflammatory diseases in man. Interestingly, MKP-1 expression and protein function have been found to be regulated by certain anti-inflammatory drugs, namely by glucocorticoids, antirheumatic gold compounds and PDE4 inhibitors, and MKP-1 has been shown to mediate many of their anti-inflammatory effects. In this Mini Review, we summarize the effect of MKP-1 in the regulation of innate and adaptive immune responses and its role as a potential anti-inflammatory drug target and review recent findings concerning the role of MKP-1 in certain anti-inflammatory drug effects.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland; Department of Clinical Pharmacology &Toxicology, University of Tampere School of Medicine, Tampere, Finland.
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D015551:Autoimmunity / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism*; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D048051:p38 Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases